Language
Country/Area
No result found
How do bacteria survive inside a host? Unveiling the mystery of endocytosis and secretion pathways!
In the microscopic world, the interactions between bacteria and hosts are full of complexity and challenges. In order to survive in the host, pathogenic bacteria secrete a series of proteins called "effector proteins", mainly through three different secretion systems: type III secretion system (T3SS), type IV secretion system (T4SS) and the type VI secretion system (T6SS). These effector proteins not only help bacteria invade host tissues, but also suppress the host's immune response, providing necessary support for bacterial survival.
Some bacteria inject only a few effector proteins, while others may inject dozens or even hundreds.
For example, if the bacterium that causes plague, such as Yersinia pestis, loses its T3SS, its pathogenicity is completely eliminated, even when it enters the bloodstream directly. In this process, Gram-negative microorganisms may also use bacterial outer membrane vesicles to transport effector proteins and pathogenic factors through membrane vesicle trafficking pathways to change the environment or attack target cells, such as at the host-pathogen interface.
Diversity of effector proteins
Many pathogenic bacteria are known to possess secreted effector proteins, but for most species the exact number remains unknown. As pathogen genomes are sequenced, effector proteins can be predicted based on protein sequence similarity, but such predictions are not always accurate. In addition, it is quite difficult to experimentally prove whether the predicted effector proteins are actually secreted into host cells, because the content of each effector protein is usually very small.
For example, Tobe et al. (2006) predicted more than 60 effector proteins for pathogenic E. coli but were able to demonstrate that only 39 of them could be secreted into human Caco-2 cells.
Even within the same bacterial species, different strains often have different repertoires of effector proteins. For example, the plant pathogenic bacterium Pseudomonas syringae had 14 effector proteins found in one strain, but more than 150 effector proteins were found in multiple different strains.
Mechanism of action
Given the diversity of effector proteins, they have different effects on various processes within cells. T3SS effector proteins of some pathogenic E. coli, Shigella, Salmonella, and Yersinia can regulate cytoskeletal dynamics, aid bacterial attachment or invasion, prevent phagocytosis, modulate apoptotic pathways, and manipulate host immune responses.
For example, phagocytes recognize and "eat" bacteria, but Yersinia inhibits phagocytosis by transporting effector proteins that inhibit the arrangement of the cytoskeleton.
During the process of endocytosis, some bacteria, such as Salmonella and Shigella, enter and survive in host cells. Salmonella manipulates the endosomal-lysosomal pathway to create a vacuolar cavity called a Salmonella-containing vacuole (SCV), which is essential for its survival inside. As SCVs mature, they migrate to the microtubule organizing center (MTOC) and generate Salmonella-initiated filaments (Sif) dependent on the T3SS effector proteins SseF and SseG. In contrast, Shigella rapidly dissolves its vacuoles through the action of the T3SS effector proteins IpaB and C.
Immune escape
Many pathogenic bacteria have also developed mechanisms to avoid the host's immune response. Taking EPEC/EHEC as an example, its effector protein EspG can reduce the secretion of interleukin-8 (IL-8), thereby affecting the host's immune system. EspG functions as a Rab GTPase-activating protein (Rab-GAP), which causes Rab-GTPases to fall into an inactive GDP-bound state, thereby reducing the process of ER-homoglia transport.
In addition, pathogenic bacteria also have the ability to prevent host cell apoptosis, thereby maintaining their living environment.
For example, the EPEC/EHEC effector proteins NleH and NleF prevent apoptosis, and the Shigella effector proteins IpgD and OspG prevent apoptosis by phosphorylating and stabilizing the MDM2 protein. Salmonella inhibits host cell apoptosis and activates survival signals by relying on the effector proteins AvrA and SopB.
Immune Response Effects
Human cells are able to recognize pathogen-associated molecular patterns (PAMPs). When bacteria bind to these receptors, signal transduction pathways such as NF-kB and MAPK pathways are activated, which leads to the release of cytokines and proteins that regulate immune responses. factor. Many bacterial effector proteins affect NF-kB signaling. For example, the EPEC/EHEC effector proteins NleE, NleB, NleC, NleH, and Tir are immunosuppressive effector proteins that primarily target proteins in the NF-kB signaling pathway.
NleC was shown to cleave the NF-kB p65 pair, thereby inhibiting IL-8 production.
With the deepening of research on bacterial effector proteins, scientists have also proposed many relevant databases and online resources to assist in the prediction and functional analysis of bacterial effector proteins.
As these microscopic processes are gradually revealed, we can't help but wonder: In this long-term game between host and pathogen, how can humans continue to improve our defense mechanisms to cope with possible pathogenic challenges in the future?
